Syntheses of quaternary carbon-containing oxazatricycle and spiropyran libraries via multicomponent reactions and their molecular switching properties

Article abstract of DOI:10.1021/cc900127g

A practical protocol for the preparation of parallel solution-phase libraries of the quaternary carbon-containing oxazatricycles and spiropyrans is reported. Target compounds were obtained in moderate to excellent yields by an Et₃N-mediated mul

Full text of DOI:10.1021/cc900127g

J. Comb. Chem. 2010, 12, 119–124
119
Syntheses of Quaternary Carbon-Containing Oxazatricycle and
Spiropyran Libraries via Multicomponent Reactions and Their
Molecular Switching Properties
Chi-Hui Lin, Jhih-Rong Chen, and Ding-Yah Yang*
Department of Chemistry, Tunghai UniVersity, Taichung 407, Taiwan
ReceiVed August 20, 2009
A practical protocol for the preparation of parallel solution-phase libraries of the quaternary carbon-containing
oxazatricycles and spiropyrans is reported. Target compounds were obtained in moderate to excellent yields
by an Et3N-mediated multicomponent reaction from various N-methylisoquinolium or flavylium salts and
4-hydroxycoumarins or dimedone in acetone. Purification of the final products by recrystallization in ethyl
acetate/methylene chloride or by column chromatography allowed easy isolation of nine compounds of
each array. Preliminary studies indicated that some of the prepared compounds exhibit redox switching,
photochromic, and thermochromic properties.
Introduction
quaternary carbon source. Their molecular switching proper-
ties are also investigated.
Multicomponent reactions (MCRs)1 are convergent reac-
tions, in which three or more starting materials react to form
a product, where all or most of the atoms contribute to the
newly generated product. The MCRs represent an attractive
synthetic strategy for a rapid and efficient library generation
due to the fact that the products are formed in a single step,
and the diversity can be achieved simply by varying the
reacting components. After intensive research for the past
decade, many different backbone libraries have become
accessible. While majority of the available libraries were
prepared mainly for their potential biological activities and
therapeutic applications, few were aimed at developing of
novel organic molecular switches. Molecular switches are
molecules that can be transformed into two or more stable
states by an external stimulus such as pH, light, temperature,
or redox potential. Compounds with molecular switching
properties may have wide applications in a number of fields
including nanotechnology2 and biology.3 Recently, we
reported a one-pot tandem four-component reaction for
preparation of an oxazabicycle library.4 After screening
approximately 20 compounds, the oxazabicycles 15 and 26
were found to possess photochromic and fluorescence redox
switching properties, respectively (Figure 1). This successful
experience prompted us to believe that novel molecular
switches may potentially be screened from heterocycle
libraries generated by new MCRs. To test this speculation,
along with our continuing efforts to develop new molecular
scaffolds to function as backbones for organic functional
materials, we describe here two parallel solution-phase
syntheses of the gem-dimethyl-substituted quaternary carbon-
containing oxazatricycles and spiropyrans by an Et3N-
mediated three-component reaction using acetone as a
Results and Discussion
The target oxazatricycles and spiropyrans were obtained,
as indicated in Scheme 1, in a one-pot reaction by mixing
N-methylisoquinolium or flavylium salts and 4-hydroxycou-
marins or dimedone in the presence of triethylamine in
acetone under reflux conditions for 8 and 0.5 h, respectively.
After the reaction was quenched with water, the products
were extracted with methylene chloride, dried in MgSO4,
concentrated in vacuo, and subsequently purified by recrys-
Figure 1. Structures of two oxazabicycles that possess molecular
switching properties screened from MCRs.
Scheme 1. Preparation of the Oxazatricycle 1a and
Spiropyran 2a Using a Three-Component Reaction
* To whom correspondence should be addressed. Phone: 886-4-2359-
7613. Fax: 886-4-2359-0426. E-mail: yang@thu.edu.tw.
10.1021/cc900127g CCC: $40.75  2010 American Chemical Society
Published on Web 10/27/2009

120 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1
Lin et al.
Figure 2. Oxazatricycle library products 1a-1i obtained by a parallel three-component reaction.
Figure 3. Spiropyran library products 2a-2i obtained by a parallel three-component reaction.
tallization in ethyl acetate/methylene chloride or flash column
chromatography. Figures 2 and 3 list the structures of nine
compounds of each generated array with the yield given
underneath, which demonstrated the versatility of this one-
pot reaction through the three-component preparation of
libraries of oxazatricycles and spiropyrans. The N-methyl-
isoquinolium iodides were synthesized by refluxing corre-
sponding substituted isoquinolines with the methyl iodide
in benzene, whereas the flavylium salts were prepared by
acid-mediated condensation7 of substituted phenol and ben-
zoylacetone in ethyl acetate under room temperature. 7-Di-
methylamino-4-hydroxycoumarin used for the synthesis of
compounds 1b, 1e, 1h, and 2c-2f was prepared according
to the literature procedure.8 It can be observed that both
MCRs gave lower yields for dimedone, moderate yields for
4-hydroxycoumarin, and better yields for 7-dimethylamino-
4-hydroxycoumarin. The higher yields for the latter is
presumably due to the presence of an electron-donating
dimethylamino group at the 7-position of the coumarin
moiety.
The structural assignment of the prepared oxazatricycles
and spiropyrans was based on spectroscopic data (1H, 13C
1
NMR, HRMS). In the H NMR spectra, two distinctive
bridgehead hydrogen absorption peaks for the oxazatricyclic
ring were observed at the chemical shifts of 3.43-3.86 and
2.65-3.01 ppm for all prepared compounds 1a-1i, whereas
characteristic AB quartet absorption peaks for methylene
hydrogens on the spiropyran ring were detected around
2.47-2.41 and 2.25-1.96 ppm with a coupling constant of
14.4 Hz for compounds 2a-2i. Some of the heterocyclic

Oxazatricycle and Spiropyran Libraries
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1 121
Figure 4. X-ray crystal structures of the oxazatricycle 1d and spiropyran 2e.
Scheme 2. Proposed Mechanisms for the Formation of the
Oxazatricycle 1a and Spiropyran 2a
Scheme 3. Fluorescence Redox Switches between the
Oxazatricycle 1b and Zwitterion 8
the tertiary alcohol 7. The subsequent coupling of 7 with
4-hydroxycoumarin yielded the spiropyran 2a.11 Similar
to the oxazatricycle 1a, the bond formation during the
construction of the spiropyran skeleton is also efficient
and atom-economical, with overall formation of two C-C
bonds and one C-O bond.
structures were further elucidated by single-crystal X-ray
diffraction analysis. Figure 4 shows the ORTEP diagrams
of the oxazatricycle 1d and spiropyran 2e, which clearly
revealed a rigid oxazatricyclic skeleton and a spiropyran
moiety, respectively.9
With the availability of these two libraries, their molecular
switching properties were then investigated. Some of the
oxazatricycles were found to exhibit fluorescence redox
switching properties. For instance, the oxazatricycle 1b
emitted strong fluorescence in methanol. Addition of sodium
borohydride to 1b induced the ring-opening of the oxaza-
tricyclic moiety to generate the weakly fluorescent zwitter-
ionic species 8, which can be swiftly reverted to 1b by 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation in
methylene chloride (Scheme 3). For the spiropyran library,
some exhibit photochromic properties, others show thermo-
chromic properties. As depicted in Schemes 4 and 5, while
the colorless spiropyran 2a is sensitive to light and converts
to the green zwitterion 9 upon UV irradiation, the colorless
spiropyran 2b, in the presence of an external proton donor
such as imidazole, is sensitive to heat and changes to the
purple ring-opened form 10 when temperature is increased.
Although the molecular switching properties of these com-
pounds merit further investigations,12 the present studies have
The proposed mechanisms for the two MCRs are
depicted in Scheme 2. Albeit both MCRs utilize acetone
as a gem-dimethyl-substituted quaternary carbon source
to construct the heterocyclic scaffolds, their reaction
mechanisms are considerably different. For the oxazatri-
cycle 1a, it began with an equilibrium-driven, inverse-
electron demand aza-Diels-Alder reaction of acetone
enolate and isoquinolium salt to give the iminium-
containing cycloadduct 6.10 The second step involved a
nonequilibrium trapping of 6 with 4-hydroxycoumarin to
afford the oxazatricycle 1a. It is worth mentioning that
the bond formation for the construction of the tricyclic
skeleton is not only highly efficient with the formation of
three C-C bonds and one C-O bond but also regiose-
lective and stereospecific, creating a tricyclic system
containing four chiral centers. For the spiropyran 2a, it
involved first deprotonation of flavylium salt 5 by triethyl-
amine and followed by reacting with acetone to afford

122 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1
Lin et al.
Scheme 4. Photochromic Switches between the Spiropyran
2a and Zwitterions 9
silica gel 60G-254 plates (25 mm) and developed with the
solvents mentioned. Flash chromatography was performed
in columns of various diameters with Merck silica gel
(230-400 mesh ASTM 9385 kieselgel 60H) by elution with
the solvent systems. Solvents, unless otherwise specified,
were reagent grade and distilled once prior to use.
General Procedure for 1a-1i. To a solution of N-
methylisoquinolium iodide (0.50 mmol) in acetone (10 mL)
was added 4-hydroxycoumarin (0.50 mmol) and a catalytic
amount of triethylamine. The resulting solution was refluxed
for 8 h. After completion of the reaction, the mixture was
cooled to room temperature and then the solvent was
concentrated in vacuo. The residue was poured into water,
and the product was extracted twice with methylene chloride.
The combined organic extracts were dried over MgSO4,
filtered, and concentrated. The resulting crude product was
recrystallized in ethyl acetate/methylene chloride to give the
product.
Scheme 5. Thermochromic Switches between the Spiropyran
2b and Ring-Opened Form 10
Preparation of 1a: white solid; yield 82%; Rf ) 0.55
(15% EtOAc/hexanes); mp 184-186 °C; 1H NMR (CDCl3,
300 MHz) δ 7.85 (dd, J ) 6.6, 1.5 Hz, 1H), 7.48-7.54 (m,
1H), 7.31-7.19 (m, 6H), 4.61 (d, J ) 3.0 Hz, 1H), 3.63 (d,
J ) 3.6 Hz, 1H), 2.98 (d, J ) 3.0 Hz, 1H), 2.46 (s, 3H),
2.48-2.42 (m, 1H), 1.51 (dd, J ) 12.9, 1.2 Hz, 1H), 1.37
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 161.0, 156.0, 152.7,
140.0, 134.5, 131.1, 127.22, 127.21, 127.0, 123.4, 123.1,
122.9, 116.1, 115.9, 110.0, 93.6, 56.5, 45.5, 43.9, 42.5, 27.3,
24.5; IR ν (KBr) 2903, 1699, 1620, 1572, 1397 cm-1; HRMS
(FAB) calcd for C22H20NO3 [M + H] 346.1443, found
346.1446.
clearly demonstrated the feasibility of discovering of novel
molecular switches from new MCRs-generated libraries.
Conclusions
In summary, two practical parallel solution-phase syntheses
of the oxazatricycles and spiropyrans using an Et3N-
mediated, one-pot reaction are developed. Purification of the
final products can be accomplished by either recrystallization
in ethyl acetate/methylene chloride or column chromato-
graphy with moderate to excellent yields. Our protocol for
these three-component reactions provides a quick access to
the gem-dimethyl-substituted quaternary carbon-containing
oxazatricycles and spiropyrans with diverse substitution
patterns using acetone as a quaternary carbon source.
Moreover, some of the prepared compounds were found to
possess molecular switching properties such as fluorescence
redox switch, photochromism, and thermochromism. We
have demonstrated that novel molecular switches can be
discovered by screening of new heterocycle libraries gener-
ated by MCRs.
Preparation of 1b: white solid; yield 93%; Rf ) 0.58
(25% EtOAc/hexanes); mp 198-199 °C; 1H NMR (CDCl3,
300 MHz) δ 7.64 (d, J ) 9.0 Hz, 1H), 7.29-7.19 (m, 4H),
6.59 (dd, J ) 9.0, 2.1 Hz, 1H), 6.45 (d, J ) 2.1 Hz, 1H),
4.53 (d, J ) 3.0 Hz, 1H), 3.63 (d, J ) 3.9 Hz, 1H), 3.01 (s,
6H), 2.95 (d, J ) 3.0 Hz, 1H), 2.48 (s, 3H), 2.48-2.42 (m,
1H) 1.47 (d, J ) 12.6 Hz, 1H), 1.35 (s, 3H); 13C NMR
(CDCl3, 75 MHz) δ 161.9, 157.0, 154.7, 152.6, 139.7, 135.0,
127.1, 127.0, 127.0, 123.5, 123.0, 108.3, 105.4, 104.9, 97.2,
93.2, 56.8, 45.7, 44.0, 42.6, 40.0, 26.9, 24.9; IR ν (KBr)
2910, 1702, 1602, 1407, 1102 cm-1; HRMS (FAB) calcd
for C24H25N2O3 [M + H] 389.1865, found 389.1862.
Preparation of 1c: white solid; yield 65%; Rf ) 0.51 (15%
1
EtOAc/hexanes); mp 137-138 °C; H NMR (CDCl3, 300
Experimental Section
MHz) δ 7.28-7.24 (m, 3H), 7.23-7.14 (m, 1H), 4.29 (d, J
) 3.0 Hz, 1H), 3.55 (dd, J ) 4.8, 1.5 Hz, 1H), 2.78 (d, J )
3.0 Hz, 1H), 2.39-2.38 (m, 4H), 2.28-2.19 (m, 4H), 1.35
(dd, J ) 13.2, 1.5 Hz, 1H), 1.19 (s, 3H), 1.11 (s, 3H) 1.08
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 196.5, 164.7, 139.8,
135.1, 126.825, 126.824, 123.0, 119.4, 92.8, 56.9, 51.6, 45.9,
43.6, 42.7, 42.627, 42.625, 31.0, 29.7, 26.6, 26.2, 25.3; IR
ν (KBr) 2948, 1639, 1459, 1353, 1147 cm-1; HRMS (FAB)
calcd for C21H26NO2 [M + H] 324.1964, found 324.1966.
Preparation of 1d: white solid; yield 81%; Rf ) 0.58
(15% EtOAc/hexanes); mp 184-186 °C; 1H NMR (CDCl3,
300 MHz) δ 7.85 (dd, J ) 8.1, 1.8 Hz, 1H), 7.48-7.45 (m,
1H), 7.33-7.21 (m, 6H), 4.63 (d, J ) 3.0 Hz, 1H), 3.0 (d,
J ) 3.0 Hz, 1H), 2.34 (s, 3H), 2.24, 1.44 (ABq, J ) 13.2
Hz, 1H each), 1.51 (s, 3H), 1.35 (s, 3H); 13C NMR (CDCl3,
Melting points were determined on a Mel-Temp melting
1
point apparatus in open capillaries and are uncorrected. H
and 13C NMR spectra were recorded at 300 and 75 MHz on
a Varian VXR300 spectrometer. Chemical shifts were
reported in parts per million on the δ scale relative to an
internal standard (tetramethylsilane, or appropriate solvent
1
peaks) with coupling constants given in hertz. H NMR
multiplicity data are denoted by s (singlet), d (doublet), t
(triplet), q (quartet), and m (multiplet). MS were performed
on JEOL JMS-SX/SX 102A spectrometer. IR spectra were
obtained using a 1725XFT-IR spectrophotometer. Single-
crystal structures were determined by a Bruker AXS
SMART-1000 X-ray single-crystal diffractometer. Analytical
thin-layer chromatography (TLC) was carried out on Merck

Oxazatricycle and Spiropyran Libraries
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1 123
75 MHz) δ 161.1, 156.2, 152.7, 141.6, 135.0, 131.2, 127.2,
127.1, 126.9, 123.4, 123.0, 121.1, 116.3, 116.0, 110.3, 94.7,
54.4, 52.1, 45.6, 38.8, 29.2, 24.6, 19.2; IR ν (KBr) 2964,
1697, 1616, 1568, 1350 cm-1; HRMS (FAB) calcd for
C23H22NO3 [M + H] 360.1600, found 360.1596.
119.1, 93.2, 58.4, 52.9, 52.8, 43.8, 41.3, 36.3, 31.4, 31.2,
28.0, 27.9, 25.8, 25.7, 22.5; IR ν (KBr) 2809, 1648, 1434,
1323, 1213 cm-1; HRMS (FAB) calcd for C22H28NO2 [M
+ H] 338.2120, found 338.2117.
General Procedure for 2a-2i. To a solution of flavylium
salt 5 (0.5 mmol) in acetone (15 mL) was added triethylamine
(0.5 mmol) and 4-hydroxycoumarin (0.6 mmol). The result-
ing solution was refluxed for 0.5 h. After completion of the
reaction, the mixture was cooled to room temperature and
then the solvent was concentrated in vacuo. The residue was
poured into water and the product was extracted twice with
methylene chloride. The combined organic extracts were
dried over MgSO4, filtered, and concentrated. The crude
product was purified by column chromatography to give the
product.
Preparation of 2a: white solid; yield 50%; Rf ) 0.50
(10% EtOAc/hexanes); mp 123-124 °C; 1H NMR (CDCl3,
300 MHz) δ 7.77 (dd, J ) 7.8, 1.5 Hz, 1H), 7.71-7.67 (m,
2H), 7.60 (dd, J ) 8.1, 1.8 Hz, 1H), 7.51-7.15 (m, 9H),
5.91 (s, 1H), 2.46, 2.22 (ABq, J ) 14.4 Hz, 1H each), 1.74
(s, 3H), 1.50 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 161.1,
158.0, 152.4, 150.4, 148.9, 133.0, 131.5, 129.5, 129.4, 128.5,
126.9, 125.1, 124.2, 123.5, 123.4, 123.1, 116.7, 116.1, 116.0,
108.6, 97.8, 74.4, 53.6, 31.5, 29.7, 27.8; IR ν (KBr) 2968,
1695, 1592, 1524, 1394 cm-1; HRMS (FAB) calcd for
C28H23O4 [M + H] 423.1581, found 423.1583.
Preparation of 2b: white solid; yield 51%; Rf ) 0.30
(15% EtOAc/hexanes); mp 158-159 °C; 1H NMR (CDCl3,
300 MHz) δ 7.77 (dd, J ) 7.8, 1.5 Hz, 1H), 7.62 (dd, J )
8.1, 1.8 Hz, 1H), 7.51-7.41 (m, 3H), 7.33-7.16 (m, 5H),
7.10 (s, 1H), 7.00-6.90 (m, 2H), 6.02 (s, 1H), 2.46, 2.25
(ABq, J ) 14.4 Hz, 1H each), 1.75 (s, 3H), 1.50 (s, 3H);
13C NMR (CDCl3, 75 MHz) δ 158.8, 154.5, 152.3, 149.9,
147.7, 132.4, 131.7, 130.8, 129.7, 127.8, 127.1, 124.6, 123.9,
123.6, 122.9, 120.3, 118.9, 117.2, 116.5, 116.1, 108.6, 101.1,
91.2, 74.3, 53.5, 31.6, 29.8, 27.8; IR ν (KBr) 3233, 2981,
1669, 1612, 1564 cm-1; HRMS (FAB) calcd for C28H23O5
[M + H] 439.1545, found 439.1548.
Preparation of 2c: white solid; yield 61%; Rf ) 0.25
(10% EtOAc/hexanes); mp 128-129 °C; 1H NMR (CDCl3,
300 MHz) δ 7.77 (dd, J ) 7.8, 1.5 Hz, 1H), 7.71-7.67 (m,
2H), 7.60 (dd, J ) 8.1, 1.8 Hz, 1H), 7.51-7.15 (m, 9H),
5.91 (s, 1H), 2.46, 2.22 (ABq, J ) 14.4 Hz, 1H each), 1.74
(s, 3H), 1.50 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 162.1,
159.1, 154.4, 152.8, 150.4, 148.6, 133.1, 129.5, 129.3, 128.4,
126.9, 125.1, 124.1, 123.6, 116.6, 108.4, 108.3, 105.0, 103.9,
98.4, 97.3, 73.9, 53.8, 40.1, 40.0, 31.2, 29.9, 28.0; IR ν (KBr)
2916, 1695, 1617, 1597, 1503 cm-1; HRMS (FAB) calcd
for C30H28NO4 [M + H] 466.2018, found 466.2014.
Preparation of 2d: white solid; yield 52%; Rf ) 0.18
(15% EtOAc/hexanes); mp 141-142 °C; 1H NMR (CDCl3,
300 MHz) δ 7.63 (dd, J ) 7.8, 1.5 Hz, 1H), 7.55 (d, J )
9.0 Hz, 1H), 7.45-7.20 (m, 5H), 7.13 (s, 1H), 6.99-6.88
(m, 2H), 6.51 (dd, J ) 9.0, 2.4 Hz, 1H), 6.47 (d, J ) 2.4
Hz, 1H), 6.00 (s, 1H), 3.01 (s, 6H), 2.41, 2.20 (ABq, J )
14.4 Hz, 1H each), 1.71 (s, 3H), 1.47 (s, 3H); 13C NMR
(CDCl3, 75 MHz) δ 162.6, 159.4, 154.6, 154.4, 152.8, 149.9,
147.3, 130.7, 129.4, 127.8, 127.1, 124.4, 124.1, 123.6, 120.1,
119.1, 117.2, 116.3, 108.6, 105.0, 103.9, 102.0, 97.3, 73.6,
Preparation of 1e: white solid; yield 90%; Rf ) 0.53 (25%
1
EtOAc/hexanes); mp 199-201 °C; H NMR (CDCl3, 300
MHz) δ 7.63 (d, J ) 8.7 Hz, 1H), 7.32-7.29 (m, 3H),
7.22-7.19 (m, 1H), 6.58 (dd, J ) 9.0, 1.5 Hz, 1H), 6.47 (s,
1H), 4.55 (d, J ) 2.7 Hz, 1H), 3.01 (s, 6H), 2.96 (d, J ) 2.4
Hz, 1H), 2.33 (s, 3H), 2.42, 1.41 (ABq, J ) 12.9 Hz, 1H
each), 1.50 (s, 3H), 1.35 (s, 3H); 13C NMR (CDCl3, 75 MHz)
δ 162.0, 157.2, 154.7, 152.6, 141.6, 135.4, 127.0, 126.9,
126.8, 123.7, 121.1, 108.4, 105.7, 105.1, 96.3, 94.3, 54.5,
52.2, 45.8, 40.1, 38.8, 28.9, 24.9, 19.2; IR ν (KBr) 2868,
1602, 1570, 1460, 1377 cm-1; HRMS (FAB) calcd for
C25H27N2O3 [M + H] 403.2022, found 403.2019.
Preparation of 1f: white solid; yield 62%; Rf ) 0.58 (25%
1
EtOAc/hexanes); mp 135-136 °C; H NMR (CDCl3, 300
MHz) δ 7.28-7.21 (m, 3H), 7.18-7.15 (m, 1H), 4.30 (d, J
) 3.0 Hz, 1H), 2.80 (d, J ) 3.0 Hz, 1H), 2.39 (d, J ) 17.4
Hz, 1H), 2.28-2.22 (m, 6H), 2.02, 1.30 (ABq, J ) 12.9
Hz, 1H each), 1.45 (s, 3H), 1.18 (s, 3H), 1.11 (s, 3H), 1.07
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 196.5, 164.9, 141.5,
135.4, 126.6, 127.0, 120.9, 119.6, 93.8, 54.3, 51.9, 51.5, 45.9,
42.428, 42.425, 38.8, 31.0, 29.6, 28.1, 26.6, 25.2, 19.1; IR
ν (KBr) 2937, 1642, 1468, 1353, 1028 cm-1; HRMS (FAB)
calcd for C22H28NO2 [M + H] 338.2120, found 338.2122.
Preparation of 1g: white solid; yield 83%; Rf ) 0.55
(15% EtOAc/hexanes); mp 190-191 °C; 1H NMR (CDCl3,
300 MHz) δ 7.84 (dd, J ) 7.8, 1.2 Hz, 1H), 7.48-7.43 (m,
1H), 7.29-7.16 (m, 6H), 3.57 (d, J ) 3.9 Hz, 1H), 2.80 (s,
1H), 2.40 (dd, J ) 12.9, 4.8 Hz, 1H), 2.39 (s, 3H), 1.41 (dd,
J ) 12.9, 1.2 Hz, 1H), 1.37 (s, 3H), 1.14 (s, 3H); 13C NMR
(CDCl3, 75 MHz) δ 161.2, 155.9, 152.6, 139.7, 135.6, 130.9,
127.4, 127.0, 123.2, 122.8, 122.6, 116.2, 115.8, 109.5, 94.6,
57.8, 52.3, 44.0, 36.2, 29.5, 28.9, 24.8, 22.1; IR ν (KBr)
2953, 1697, 1625, 1397, 1066 cm-1; HRMS (FAB) calcd
for C23H22NO3 [M + H] 360.1600, found 360.1596.
Preparation of 1h: white solid; yield 90%; Rf ) 0.53
(25% EtOAc/hexanes); mp 177-178 °C; 1H NMR (CDCl3,
300 MHz) δ 7.63 (d, J ) 8.7 Hz, 1H), 7.23-7.28 (m, 3H),
7.16-7.18 (m, 1H), 6.58 (dd, J ) 8.7, 2.4 Hz, 1H), 6.47 (d,
J ) 2.4 Hz, 1H), 3.57 (d, J ) 4.2 Hz, 1H), 3.01 (s, 6H),
2.77 (s, 1H), 2.45 (dd, J ) 12.6, 4.2 Hz, 1H), 2.38 (s, 3H),
1.41 (dd, J ) 12.6, 1.2 Hz, 1H), 1.35 (s, 3H), 1.11 (s, 3H);
13C NMR (CDCl3, 75 MHz) δ 162.2, 157.0, 154.7, 152.5,
139.9, 136.1, 127.5, 126.9, 126.8, 123.5, 122.6, 108.3, 105.2,
105.2, 97.3, 94.0, 58.2, 52.6, 44.1, 40.1, 36.2, 28.6, 25.2,
22.3; IR ν (KBr) 2852, 1805, 1566, 1403, 1325 cm-1; HRMS
(FAB) calcd for C25H27N2O3 [M + H] 403.2022, found
403.2026.
Preparation of 1i: white solid; yield 64%; Rf ) 0.50 (15%
1
EtOAc/hexanes); mp 142-143 °C; H NMR (CDCl3, 300
MHz) δ 7.23-7.17 (m, 3H), 7.13-7.11 (m, 1H), 3.48 (d, J
) 3.9 Hz, 1H), 2.60 (s, 1H), 2.32 (s, 3H), 2.29-2.25 (m,
3H), 2.20, 1.27 (ABdq, J ) 12.9, 4.8 Hz, 1H each), 1.19 (s,
3H), 1.08-1.05 (m, 7H), 0.96 (s, 3H); 13C NMR (CDCl3,
75 MHz) δ 192.4 160.4, 140.5, 136.3, 126.7, 122.9, 119.6,

124 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1
Lin et al.
53.8, 40.1, 31.1, 29.9, 27.8; IR ν (KBr) 3280, 2939, 1666,
1620, 1594 cm-1; HRMS (FAB) calcd for C30H28NO5 [M
+ H] 482.1967, found 482.1966.
1.56 (s, 3H), 1.34 (s, 3H), 1.08 (s, 3H), 1.07 (s, 3H); 13C
NMR (CDCl3, 75 MHz) δ 197.5, 167.3, 160.2, 151.3, 148.5,
133.4, 129.2, 128.4, 127.7, 125.1, 117.1, 115.7, 111.6, 100.5,
98.5, 73.3, 55.4, 52.3, 43.5, 31.1, 30.7, 30.6, 29.4, 28.4, 26.6;
IR ν (KBr) 2957, 1643, 1591, 1358, 1280 cm-1. HRMS
(FAB) calcd for C28H31O4 [M + H] 431.2222, found
431.2225.
Preparation of 2e: white solid; yield 69%; Rf ) 0.30 (12%
1
EtOAc/hexanes); mp 135-136 °C; H NMR (CDCl3, 300
MHz) δ 7.70-7.66 (m, 2H), 7.53 (d, J ) 7.2 Hz, 1H), 7.47
(d, J ) 8.7 Hz, 1H), 7.42-7.32 (m, 3H), 6.83 (dd, J ) 8.7,
2.4 Hz, 1H), 6.67 (d, J ) 2.4 Hz, 1H), 6.50 (d, J ) 7.2 Hz,
1H), 6.48 (s, 1H), 5.93 (s, 1H), 3.88 (s, 3H), 3.00 (s, 6H)
2.42, 2.14 (ABq, J ) 14.4 Hz, 1H each), 1.70 (s, 3H), 1.47
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 162.1, 160.3, 159.2,
154.4, 152.7, 151.4, 148.6, 133.1, 129.2, 128.4, 127.9, 125.0,
124.1, 115.8, 111.6, 108.4, 105.1, 103.7, 100.6, 98.5, 97.2,
73.9, 55.5, 53.6, 40.0, 31.2, 29.9, 28.0; IR ν (KBr) 2926,
1695, 1618, 1597, 1384 cm-1; HRMS (FAB) calcd for
C31H30NO5 [M + H] 496.2046, found 496.2044.
Acknowledgment. We thank the National Science Council
of the Republic of China, Taiwan, for financially supporting
this research under Contract No. NSC 98-2113-M-029-003-
MY2.
Supporting Information Available. Spectral data for
1a-i, 2a-i, and the x-ray crystallographic data for 1d and
2e. This information is available free of charge via the
Internet at http://pubs.acs.org.
Preparation of 2f: white solid; Yield 62%; Rf ) 0.25
(12% EtOAc/hexanes); mp 136-137 °C;1H NMR (CDCl3,
300 MHz...) δ 7.70-7.67 (m, 2H), 7.54 (d, J ) 9.6 Hz, 1H),
7.44 (s, 1H), 7.41-7.34 (m, 3H), 6.66 (dd, J ) 8.7, 2.4 Hz,
1H), 6.52-6.47 (m, 3H), 5.91 (s, 1H), 3.03 (s, 6H), 3.00 (s,
6H), 2.44, 2.13 (ABq, J ) 14.4 Hz, 1H each), 1.70 (s, 3H),
1.48 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 162.3, 159.2,
154.5, 152.7, 151.4, 148.7, 133.6, 129.0, 128.4, 127.5, 125.1,
124.4, 123.7, 111.3, 109.2, 108.4, 105.3, 103.4, 98.6, 97.3,
91.6, 74.2, 49.1, 40.4, 40.1, 35.6, 31.3, 24.7; IR ν (KBr)
2958, 1705, 1607, 1487, 1368 cm-1; HRMS (FAB) calcd
for C32H33N2O4 [M + H] 509.2440, found 509.2443.
Preparation of 2g: white solid; yield 29%; Rf ) 0.60
(10% EtOAc/hexanes); mp 134-135 °C; 1H NMR (CDCl3,
300 MHz) δ 7.70-7.67 (m, 2H), 7.35-7.38 (m, 4H), 7.35
(dd, J ) 7.2, 2.1 Hz, 1H), 7.24-7.19 (m, 2H), 5.80 (s, 1H),
2.37-2.22 (m, 5H), 1.99 (d, J ) 14.4 Hz, 1H), 1.56 (s, 3H),
1.34 (s, 3H), 1.09 (s, 3H), 1.08 (s, 3H); 13C NMR (CDCl3,
75 MHz) δ 197.6, 167.3, 150.3, 148.5, 133.4, 129.2, 129.1,
128.5, 126.9, 125.2, 124.0, 123.5, 117.4, 116.6, 98.4, 73.3,
54.3, 52.4, 43.5, 31.2, 30.8, 30.6, 29.5, 28.4, 26.7; IR ν (KBr)
2947, 1643, 1627, 1592, 1503 cm-1; HRMS (FAB) calcd
for C27H29O3 [M + H] 401.2117, found 401.2114.
Preparation of 2h: white solid; yield 31%; Rf ) 0.55
(15% EtOAc/hexanes); mp 160-161 °C;1H NMR (CDCl3,
300 MHz) δ 7.54-7.25 (m, 5H), 7.16 (dd, J ) 8.1, 1.5 Hz,
1H), 7.02-6.92 (m, 2H), 6.00 (s, 1H), 2.31-2.24 (m, 5H),
2.02 (d, J ) 14.4 Hz, 1H), 1.57 (s, 3H), 1.35 (s, 3H), 1.09
(s, 3H), 1.06 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 198.6,
168.3, 154.8, 150.0, 146.9, 130.5, 129.3, 127.9, 127.0, 124.2,
123.4, 120.0, 119.4, 117.5, 117.0, 116.4, 102.0, 73.3, 54.1,
52.2, 43.6, 31.3, 30.7, 30.6, 29.2, 28.1, 26.9; IR ν (KBr)
3149, 2965, 1620, 1580, 1449 cm-1; HRMS (FAB) calcd
for C27H29O4 [M + H] 417.2066, found 417.2068.
References and Notes
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(9) Crystallographic data (excluding structure factors) for com-
pounds 1d and 2e have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
nos. CCDC-742565 and -665158, respectively. These data can
be obtained free of charge via www.ccdc.cam.ac.uk/data_re-
quest/cif, by emailing data_request@ccdc.cam.ac.uk, or by
contacting the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, U.K.; fax: +44 1223
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(12) The detailed fluorescence redox switching properties of 1a-
1i and the photochromic and thermochromic properties of 2a-
2i will be reported elsewhere.
Preparation of 2i: white solid; yield 35%; Rf ) 0.65 (12%
1
EtOAc/hexanes); mp 136-137 °C; H NMR (CDCl3, 300
MHz) δ 7.70-7.67 (m, 2H), 7.45-7.35 (m, 4H), 6.80 (dd,
J ) 8.7, 2.4 Hz, 1H), 6.71 (d, J ) 2.4 Hz, 1H), 5.85 (s, 1H),
3.85 (s, 3H), 2.36-2.22 (m, 5H), 1.96 (d, J ) 14.4 Hz, 1H),
CC900127G